We propose to test the hypothesis that allotype production in rabbits is controlled by specific anti-allotypic helper and suppressor cells. The role of such cells in maintaining an allotypic network will be defined using as functional probes anti-idiotype antisera against anti-allotypic antibodies and specific cellular immuno-adsorbents. Shifts in regulatory balances will be observed during normal and antigen-induced allotype production, chronic allotype suppression, and latent allotype expression. Regulatory cells and their targets will be characterized with respect to epitope specificity and T-cell/B-cell nature. We will attempt to clarify crossovers between allotypic, idiotypic and antigenic regulatory spheres. The major systems and resources to be employed are in vivo and in vitro T-dependent antibody responses and rabbits defined with respect to allotype and the major histocompatibility locus. Information obtained in the proposed study should advance our understanding of lymphocyte regulation and thus have relevance to human pathological states such as immunodeficiency, autoimmunity, allergy and cancer.